[unreadable] This proposal brings together a multi-disciplinary team with expertise in cellular and vascular biology, chemistry, material science and engineering and ultrasound to bring molecular imaging tools to ultrasound imaging. Ultrasound, the most versatile, least costly, most widely available, most practical, and only mobile imaging technology that also allows real-time imaging to guide needle placement in any visible location could benefit greatly from the ability to detect molecular targets and cellular events. Equally important, is that sonography is ideally suited to image mice, the most versatile animal model, by providing real-time imaging that can be easily performed in a sterile setting and without anesthesia. [unreadable] This proposal aims to target perfluorocarbon (RFC) liquid droplets, microbubbles and iron-oxide-containing RFC droplets to induce phase-transition to detect intra- and extra-vascular targets, label and track cells, and induce marked signal augmentation caused by endogenous enzymes or those induced by gene expression. Further, because of the local energy deposited during insonation, ultrasound agents can be used for diagnosis and with proper agent design and transmit conditions, for gene or drug delivery or even cell or tissue ablation. The advantage of RFC emulsion over microbubbles is the small droplet size (0.06-0.1 Sum) that can reach non-vascular targets, the 107 times greater blood concentration and the hours vs. minutes intravascular dwell time increasing the opportunity for interaction with receptors. Further, liquid RFC droplets act as an "ultrasound switch" since they are only visible when they accumulate at the target. However, they produce a weak signal and are difficult to detect. We aim to induce signal augmentation in 3 ways: 1) several hundred fold increase would occur when additional droplets are aggregated and >1010 increase if microbubbles are added; 2) cause aggregation and therefore an "imaging switch" only when a specific enzyme is present; and 3) incorporate iron-oxide with the RFC droplet to induce phase-transition from liquid to vapor by applying an external magnetic field as is done with hyperthermia, increasing signal by 1010 times and allowing the detection of miniscule quantities of RFC droplets. Since cells can phagocytose or take in droplets or even microbubbles, it will be possible to label and detect cells in-vivo. [unreadable] [unreadable]